Chronic peptic ulceration remains a disease which predominantly affects man. Great difficulty has been experienced in producing chronic mucosal ulcers in animals; however, there are many effective animal models for acute peptic ulceration. These can be used to test theories on the pathogenesis and prevention of mucosal ulceration and the effect of medical and surgical procedures used to treat ulcer disease. In addition, the mode of action, side effects, and comparative efficacy of drugs can be tested. Techniques that have been used in the laboratory to produce ulceration include surgical alterations of the upper gastrointestinal tract, mechanical trauma, the mucosal application of noxious agents, the exogenous and endogenous stimulation of acid secretion, or the application of stress. Great care must be exercised in extrapolating from these results, since different species show varying responses. Areas that have been studied include mucosal blood flow, acid/base balance, mucosal pH, hormones, mucosal resistance, the protective properties of mucus, ultrastructure, microvasculature, biochemical changes, oxygen-derived free radicals, the influence of the nervous system, and the ability to resist luminal noxious agents under different conditions. The most fruitful area for the future investigation of chronic peptic ulceration will remain in the clinical sphere, but valuable information can still be gained concerning the mechanisms of production and therapy of peptic ulcers by using animal models under defined laboratory conditions.